Table 1 Grading of scientific evidence (5)

1++

High quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias

1+

Well conducted meta-analyses, systematic reviews of RCTs, or RCTs with a low risk of bias

1–

Meta-analyses, systematic reviews or RCTs, or RCTs with a high risk of bias

2++

High quality systematic reviews of case–control or cohort studies or high quality case–control or cohort studies with a very low risk of confounding, bias, or chance and a high probability that the relationship is causal

2+

Well conducted case–control or cohort studies with a low risk of confounding, bias, or chance and a moderate probability that the relationship is causal

2–

Case–control or cohort studies with a high risk of confounding, bias, or chance and a significant risk that the relationship is not causal

3

Non­analytic studies, eg case reports, case series

4

Expert opinion